Autophagy is a catabolic process that relies on the cooperation of two distinct types of cellular organelles, autophagosomes and lysosomes (1). During starvation the cell expands both compartments to enhance degradation and recycling processes.
The lysosome maintains cellular homeostasis and mediates a variety of physiological processes, including cellular clearance, lipid homeostasis, energy metabolism, plasma membrane repair, bone remodeling, and pathogen defense. All these processes require an adaptive and dynamic response of the lysosome to environmental cues. Indeed, physiologic cues, such as aging and diet, and pathologic conditions, which include lysosomal storage diseases (LSDs), neurodegenerative diseases, injuries and infections may generate an adaptive response of the lysosome (34, 35, 36).
The understanding of the mechanisms that regulate lysosomal function and underlying lysosomal adaptation is still in an initial phase. A major player in the regulation of lysosomal biogenesis is the basic Helix-Loop-Helix (bHLH) leucine zipper transcription factor, TFEB (2). Among the identified TFEB transcriptional targets are lysosomal hydrolases, which are involved in substrate degradation, lysosomal membrane proteins that mediate the interaction of the lysosome with other cellular structures, and components of the vacuolar H+-ATPase (vATPase) complex, which participate to lysosomal acidification (37, 2).
WO2010/092112 refers to molecules able to enhance the cellular degradative pathway acting on the so called CLEAR element; among them TFEB is listed.